R Kerty E Cerebral vasoreactivity assessed with transcranial Doppler - PDF document

R, Kerty E. Cerebral vasoreactivity assessed with transcranial Doppler and regional cerebral blood �ow measurements. Dose, serum concentration, and Stroke1995;26(12) 2302-6. Bigal ME, Liberman JN, Lipton RB. Obesity and migraine: a population study.Neurology2006; 66(4) Settakis G, Molnár C, Kerényi L, et al. Acetazolamide as a vasodilatory stimulus in cerebrovascular diseases and in conditions affecting the cerebral Eur J Neurol2003; 10(6) 609-20. Sorteberg W, Lindegaard KF, Rootwelt K, Effect of acetazolamide on cerebral artery blood velocity and regional cerebral blood �ow in normal Acta Neurochirurg1989; 97(3-4):139-45. Huang SY, McCullough RE, McCullough RG, Usual clinical dose of acetazolamide does not alter cerebral blood �ow velocity.1988; 72(3): 315-26. Hauge A, Nicolaysen G, Thoresen M. Acute effects of acetazolamide on cerebral blood �ow in man.Acta 1983; 117(2) 233-9. Ridderstråle Y, Hanson M. Histochemical study of the distribution of carbonic anhydrase in the cat 1985; 124(4) 557-64. Gans MS. Idiopathic intracranial hypertension (IIH): Treatment and management. Medscape 2019. https://Kisabay Ak A, Tata G, Gokcay F, Celebisoy N. What is the optimal dose of acetazolamide in the treatment Neurol Asia2020; 25(1): 47-51. In literature the overall evaluation of the patients presenting to the headache outpatient clinic, it was seen that number of the patients with MRM was higher than that of patients with The equal number of patients in both groups in our study occurred by chance due to our inclusion and exclusion criteria as well as the short duration of the retrospective evaluation. The main limitation of the present study was that it was retrospective. There was no placebo arm. Placebo-controlled, randomized studies with a higher number of patients are needed to more clearly and exactly evaluate the ef�cacy of the drug. In conclusion, acetazolamide is effective for short term prophylaxis of MM. The present study is the �rst to be performed using acetazolamide for this purpose. DISCLOSURECon�ict of interest: NoneREFERENCESRasmussen BK (2001) Epidemiology of headache. 2001; 21(7) 774-7. Lipton RB, Bigal ME (2005) Migraine: epidemiology, impact, and risk factors for progression. 2005;45(Suppl 1):S3–S13.Headache Classification Committee of the International Headache Society (IHS). The International Classi�cation of Headache Disorders, 2018; 38(1): 1–211.Vetvik KG, Macgregor EA, Lundqvist C, Russell MB. Self-reported menstrual migraine in the general 2010;11(2):87-92. Vetvik KG, Macgregor EA, Lundqvist C, Russell MB. Prevalence of menstrual migraine: a population-based study. 2014; 34(4): 280-8. Marcus DA, Bernstein CD, Sullivan EA, Rudy TE. A prospective comparison between ICHD-II and probability menstrual migraine diagnostic 2010;50(4):539-50. Benedetto C.

Eicosanoids in primary dysmenorrhea, Gynecol 1989; 3(1) 71-94. Cupini LM, Matteis M, Troisi E, Calabresi P, Bernardi G, Silvestrini M. Sex-hormone-related events in migrainous females. A clinical comparative study between migraine with aura and migraine without Gould D, Kelly D, Goldstone L, Gammon J. Examining the validity of pressure ulcer risk assessment scales: developing and using illustrated J Clin 2001; 10(5): 697-706. Yalınay Dikmen P, Bozdağ M, Güneş M, Reliability and validity of Turkish version of Headache Impact Test (HIT-6) in patients with Arch Neuropsychiatr 2021; 58. DOI: 11.Ertas M, Siva A, Dalkara T, Validity and reliability of the Turkish Migraine Disability 2004; Beck AT, Epstein N, Brown G, Steer RA. An inventory for measuring clinical anxiety: psychometric properties.J Consult Clin Psychol1988;56(6) 893-7.Beck AT, Ward CH, Mendelson M, Mock J, Erbaugh J. An inventory for measuring depression.Arch Gen 1961; 4:561-71. Couturier EG, Bomhof MA, Neven AK, van Duijn NP. Menstrual migraine in a representative Dutch population sample: prevalence, disability and 2003;23(4):302-8. Vetvik KG, Russell MB. Are menstrual and nonmenstrual migraine attacks different?Curr Pain 2011; 15(5) 339-42. Granella F, Sances G, Allais G, . Characteristics of menstrual and nonmenstrual attacks in women with menstrually related migraine referred to headache Stewart WF, Lipton RB, Chee E, Sawyer J, Silberstein SD. Menstrual cycle and headache in a population Neurology2000; 55(10) 1517-23. Bigal ME, Serrano D, Buse D, Scher A, Stewart WF, Lipton RB. Acute migraine medications and evolution from episodic to chronic migraine: a longitudinal population-based study.2008; 48(8) 1157-68. Pringsheim T, Davenport WJ, Dodick D. Acute treatment and prevention of menstrually related migraine headache: evidence-based review.NeurologyD’Alessandro R, Gamberini G, Lozito A, Sacquegna T. Menstrual migraine: intermittent prophylaxis with a timed-release pharmacological formulation of dihydroergotamine.3 (Suppl 1) 156-8. Silberstein SD, Holland S, Freitag F, et al. Evidence-based guideline update: pharmacologic treatment for episodic migraine prevention in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society.Neurology2012; 78(17): 1337-45. Martin VT, Behbehani M. Ovarian hormones and migraine headache: understanding mechanisms and Mauskop A, Altura BT, Altura BM. Serum ionized magnesium levels and serum ionized calcium/ionized magnesium ratios in women with menstrual 2002; 42(4) 242-8. MacGregor EA. Migraine headache in perimenopausal Curr Pain Headache 2009; 13(5):399-403. Hagemann G, Ugur T, Schleussner E, Changes in 2011; 6(2), e14655. Dahl A, Russell D, Rootwelt K, Nyberg-Hansen Neurology Asia anti-in�ammatory drugs (NSAID), triptans, ergot derivatives, hormone replacement, magnesium, The

present study investigated the effect of acetazolamide in short-When the relationship between MC and cerebrospinal �uid (CSF) �ow is examined from a different pathophysiologic perspective, it has been shown that the increased volume and �ow rate of CSF in the late luteal phase may trigger headaches 25 Decreased volume of CSF and increased volume of the gray matter were found in the menstrual phase during which no signi�cant changes occur in progesterone levels, but when estrogen levels increase signi�cantly in the blood. In the phase following the LH surge during which estrogen level is lowest and progesterone level is highest, increased CSF �ow Studies have shown that acetazolamide, with its strong vasodilator properties, may reverse the cerebral vasoconstriction which plays a role in the pathophysiology of migraine headaches and decrease intracranial pressure by reducing increased blood �ow rate and production of CSF It does this by inhibiting carbonic anhydrase after passing the blood-brain barrier, thus producing acidosis.Due to acidosis, cerebral vessels undergo vasodilation, which increases cerebral blood �ow. This vasodilating effect of acetazolamide was observed only on It has been shown that no vasodilation occurs in the carotid and vertebral arteries when 250 mg of acetazolamide is given , but that a higher 500 mg of intravenous acetazolamide is effective.31 This change in the cerebral vessels may also occur as a consequence of the direct effect of perivascular 32 Acetazolamide may be given orally and intravenously. Its effect starts in 1 to 1.5 hours It was deemed appropriate to give our patients 500 mg of the drug twice daily based on experimental as well In the present study, 3 months of acetazolamide was given as short-term prophylaxis for MM for 5 days from two days before the predicted onset of the MC. Keeping adverse effects in mind, it was advised that the drug should be taken at half the target dose twice daily for the �rst two days of the �rst menstrual cycle. During acetazolamide use, hepatic and renal function, electrolytes, and hemogram were monitored. The most commonly observed adverse effects in our patients were dizziness and parasthesiae. Potassium citrate plus potassium bicarbonate tablets were given to patients with paresthesia during this period. Despite these measures, 15 patients in the PMM group and four in the MRM group discontinued the acetazolamide treatment because they could Evaluations were made in light of the tests performed before (month 0) and after (month 3) the treatment. At baseline and the post-treatment (month 3) evaluation, a clear improvement occurred in the VAS, MIDAS, and HIT scales individually in each group, as well as in all subjects in general, with the improvement being most prominent on the MIDAS

scale. When the pre-treatment VAS values were examined, the headache severity of the cases in the MRM group was observed to be higher, although the difference was not statistically signi�cant. Similarly, in the post-treatment evaluation, the patients in the MRM group had a more signi�cant improvement in the Similarly, it was remarkable that attack frequency was higher in the MRM group than in the PMM group at baseline. When the pre and post-treatment situations were compared, it was seen that frequency of headaches decreased in both groups with the difference being more Scoring of the HIT and MIDAS tests were evaluated. The number of patients with a HIT score above 60 and a MIDAS score above 21 before treatment was signi�cantly higher in the MRM group. It was seen that decrease in both MIDAS and HIT scores post-treatment occurred in both groups, but was more prominent in the MRM group, suggesting that remarkable improvement occurred in quality of life following the decrease in frequency and severity of pain. Acetazolamide significantly reduced the severity and frequency of headaches occurring during menstruation in both the PMM and MRM groups. The severity of headaches in the patients included in the present study was evaluated in all patients as well as between MM groups. In MRM, however, migraine attacks may occur in any period of the MC and these patients had more frequent, longer, and severe headaches during the In the MRM group, giving treatment for attacks of headache (NSAID, triptans) occurring in periods of the cycle other than menstruation suf�ced. No additional prophylaxis was needed in either group. Table 6: Comparison of HIT and MIDAS scores between the groups before and after treatment HIT GROUP 3 (%11.5)50-55; Less impact on everyday life 56-59; Significant impact on everyday life I ;&#xMin ;&#ximpa;t o;&#xn ev;ryd; y l;&#xife5;&#x.1 0;60; Max impact 15 (%58.2)3 (%11.5)3 (%11.5) MIDAS GROUP 0.0016-10; Intermediate or infrequent limitation 11-20; Average limitation 3 (%11.5)21 and above; severe limitation18 (%69.3)3 (%11.5)(*Wilcoxon’s test)MIDAS, Migraine Disability Assessment; HIT, Headache Impact Test; PMM, pure menstrual migraine; MRM, given in Table 6. Improvement occurred in both HIT and MIDAS scores, indicating increased quality of life in both groups, with the difference being more prominent in the MRM group (Table 6). When adverse effects of acetazolamide were reviewed, it was found that the most common adverse effects of acetazolamide in both the MRM and PMM groups were dizziness and paresthesia (60.8 %, 47.1 % retrospectively). There were no signi�cant difference in adverse events between the groups (p = 0.486). Other symptoms observed included fatigue (40%), dry mouth (33.3%), nausea (12%), polyuria (19.4%), anorexia (19.4%) and dysgeusia (17.6%). DISCUSSION Ac

etazolamide was administered as a short-term prophylactic treatment for MM in this study and was found to decrease severity and frequency of last longer, occur more frequently, and are more severe in patients with MM, especially in those with PMM, than in patients with non-menstrual related migraine. The prevalence of status By contrast, a study using population-based pain diaries found that there was no difference in the duration of headaches between migraine patients 17 term prophylaxis, has an important role in the treatment of MM. Medications used thus far for short-term prophylaxis include non-steroidal Table 5: Comparison of attack frequency by the groups before and after treatment ATTACK PMM Attack frequency (number of days/month) PMM Attack frequency (number of MRM Attack frequency (number of MRM Attack frequency (number of Before TreatmentAfter TreatmentBefore TreatmentAfter Treatment0-≤ 22-≤ 33(%11.5)3(%11.5)3(%11.5)3(%11.5) Table 4: Differences in average VAS, HIT and MIDAS scores by the groups PMM Difference in VAS Difference in HIT Difference in MIDAS (*Student’s T test **Wilcoxon’s test)MM, menstrual migraine; MC, menstrual cycle; PMM, pure menstrual migraine; MRM, menstrually-related migraine; VAS, visual analog scale; MIDAS, Migraine Disability Assessment; HIT, Headache Impact Test Table 3:VAS, HIT and MIDAS scores by the groups and total number of the patients before and after treatment PMM All MM VASBaseline VASVAS at the end of 3 month(0-9) 11.1 ± 13.1HIT at the end of 3 month(*Student’s T test **Wilcoxon’s test)MM, menstrual migraine; MC, menstrual cycle; PMM, pure menstrual migraine; MRM, menstrually-related migraine; VAS, visual analog scale; MIDAS, Migraine Disability Assessment; HIT, Headache Impact Test In regard to baseline VAS scores, there was no signi�cant difference between the groups (p = 0.342). It was remarkable that baseline VAS scores were higher in the MRM group. Our patients were analysed by headache type with respect to functional status at baseline (month 0) and after treatment (month 3). There was a statistically signi�cant difference between the baseline and �nal mean VAS, MIDAS, and HIT scores in the PMM and MRM groups individually as well as in the entire study group (p < 0.001). A decrease in the frequency of the headaches was observed, and an improvement in quality of life occurred in both groups (Table 3).Inter-group differences between mean VAS, MIDAS, and HIT scores at baseline (month 0) and post-treatment (month 3) were evaluated (Table 4). MIDAS scores were signi�cantly different between the PMM and MRM groups (p = 0.033) but VAS and HIT scores were not different (VAS: p = 0.180, HIT: p = 0.146). It was observed that remarkable improvement occurred post-treatment in all scores, with the most prominent improvement being in the MIDAS score (Ta

ble 4). The frequency of headaches in the PMM and MRM groups before and after treatment (months 0 and 3) is given in Table 5It was seen that a decrease occurred in the frequency of attacks in both groups, which was greater in the MRM group (Table 5). Details of HIT and MIDAS scores in the PMM and MRM groups before and after treatment are Table 2:Presentation, features, triggers and associated symptoms of the headached by the groups and total number of the patients Presentation of 11 (%42.3)3 (%11.5)11 (%21.2)Headache triggers Fatigue Alcohol Fasting Odor Loud noise High-intensity light Features of 3 (%11.5)Lightning Sudden 3 (%11.5)Associated symptoms Nausea Vomiting VertigoAllodynia TinnitusNausea (Student’s T test) between the MM groups (p = 0.480). In regard to family history, migraine was present 26.6% of the PMM group and in 34.2% of the MRM group (p = 0.262) In the evaluation of the presentation, triggers, features, and associated symptoms of headache, no signi�cant difference was found between MM groups (p=0.681, p=0.321, p=0.988, and p=0.173, respectively) (Table 2). VAS, MIDAS, and HIT scores according to MM type before and after acetazolamide treatment are shown in Table 3. the �rst two days of the �rst menstrual period. Acetazolamide was subsequently given at a dose of 250 mg twice daily (500 mg daily) for 5 days starting two days before the predicted onset of the second and third menstrual periods. Adverse effects were noted. Acetazolamide was given with plenty of water and food, and potassium citrate plus potassium bicarbonate tablets were started in the event of symptoms of paresthesia. Routine biochemistry investigations for renal and hepatic function as well as blood counts were performed. VAS was used to determine the severity of headache before (month 0) and after (month 3) treatment, and MIDAS and HIT tests were performed to determine the frequency of headaches and their impact on quality of life. Statistical analyses The data were analyzed using the IBM SPSS version 23 program. The normality of the distribution of data was determined using the Shapiro-Wilk test. In comparing the parameters between the groups, the independent two-sample t-test was used for data showing a normal distribution, and the Mann-Whitney U test was used for those not showing a normal distribution. To evaluate changes over time, the paired two-sample t-test and Wilcoxon’s test were used for data with and without a normal distribution respectively. Pearson’s correlation coef�cient was used to examine the correlations among the quantitative variables with a normal distribution, and Spearman’s rho correlation coef�cient was used for non-parametric data. Chi-square and Fisher’s exact tests were used to compare the categorical variables by groups. The results of the analyses are presented as

mean ± standard deviation (SD) and median (minimum – maximum) for quantitative data and as frequency (percentage) for categoric variables. The signi�cance level was set at p < 0.05. RESULTSThe neurologic examination, fundoscopic �ndings and imaging investigations of all patients included in the study were normal. The age at onset of MM and MC and age at the time of presentation to the outpatient clinic are summarized in total and groups in Table 1. No signi�cant differences were found between the PMM and MRM groups in age at the time of presentation to the outpatient clinic (p = 0.273) or age at the onset of MM (p = 0.441) and MC (p = 0.529). No statistically signi�cant relationship was found between age at the onset of MM (years) and frequency of MM (days per month) (p=0,369 r=0,127) and no relationship was found between age of onset of MM and the severity of headaches (p=0,488 r=0,098). (Table 1.) In regard to BMI, 61.5% of the patients had normal BMI, 28.8% were overweight, and 9.7% were obese. BMI was not associated with signi�cant differences (p 0.457) in headache type. Concerning the educational level of the patients, most of the patients had a university education (30.8%) or a Master’s degree (28.8%). Educational levels were not signi�cantly different Table 1:Educational level and evaluation of the age at the time of onset of MM and MC based on the groups and total number of the patients Age at the time of presen13.4 ± 1.3 (11 - 16)13.5 ± 1.3 (11 - 16)(Student’s T test) MM, menstrual migraine; MC, menstrual cycle; PMM, pure menstrual migraine; MRM, menstrually-related migraine Department of the Medical Faculty of Celal Bayar University with headache and diagnosed with MM were retrospectively reviewed after obtaining approval from the Celal Bayar University Medical School Ethics Committee (No.: 85252386-050.04.04, Date: 07.10.2019; Clinical Investigations Ethics Committee). One hundred and six patients with MM were included in the study after identifying patients with a diagnosis of headache between 2015 and A total of 54 patients were excluded from the study, 35 because of loss to follow-up (PMM:10, MRM:25) and 19 because of intolerance and non-compliance to the acetazolamide within the �rst month (PMM:4 MRM:15). The medical data of 52 remaining patients comprising 26 patients with PMM and 26 with MRM was analyzed(Figure 1). The inclusion criteria were: diagnosis of MM according to ICHD-3 and a regular MC (interval The exclusion criteria were: patients with chronic migraine according to ICHD-3, tension headache, cluster headache, other primary and secondary headaches; patients with other neurologic diseases and other chronic diseases; use of combined oral contraceptives (COC) or other exogenous hormone therapies; lactation and pregnancy; concurrent use of other

short or long-term prophylactic drugs; intermediate to high levels of depression and anxiety based on Beck’s Anxiety and Beck’s DepressionThe responses of patients to questions regarding characteristics of their headaches and the contents of their headache diaries were recorded when they attended the outpatient clinicThe headache data elicited included demographic characteristics (age at the time of presentation, age at the time of menstruation, age at the onset of MM, body-mass index [BMI], educational status); features in the medical and family history; presentation, location, triggers and features of the headache; absence of aura as well as the number of days with headache in a month. HIT-6 and MIDAS test scores, VAS scores, previously used symptomatic and prophylactic medications as well as �ndings in the neurologic and fundoscopic examination were also obtained. VAS scores measured from 0 to 10 were collected from the records. The frequency of the headaches was determined from HIT (monthly) MIDAS (three-monthly) scores and headache diaries. Patients were divided into groups according to body mass index. Those with a BMI of 20-25kg/ were classi�ed as normal, those with a BMI of 25-30 kg/m as overweight, and those with a To exclude secondary headaches, either cranial computed tomography (CT) or cranial magnetic resonance imaging (MRI) was performed in all subjects. Cranial CT angiography was performed because vascular conditions (i.e., arteriovenous malformation, aneurysm) are possible causes for continuous unilateral headaches. For short term prophylaxis, acetazolamide was started at a dose of 125 mg twice daily for Figure 1. Flow chart showing recruitment of study patientsmigraine (MM) between 2015 and 2020 were identi�ed Number of cases with pure menstrual migraine (PMM):40Number of cases of menstrual related migraine (MRM):66 The patients not regularly attending on the visits The patients intolerance to the acetazolamide within the �rst month – not regularly using the 52 patients using acetazolamide regularly and attending on the visits were included Role of acetazolamide in treatment of patients with menstrual migraine Aysin Kisabay Ak, Department of Neurology, Department of Public Health, Celal Bayar University, Manisa, Turkey Abstract According to the ICHD-3 criteria, menstrual migraine (MM) is divided into two groups: pure menstrual migraine (PMM) and menstrually-related migraine (MRM). The present study aimed to evaluate and compare the severity of headache using a visual analog scale (VAS) and the effect on quality of life using the Headache Impact Test (HIT) and Migraine Disability Assessment (MIDAS) tests Patients who presented to the headache outpatient clinic of the neurology department with a diagnosis of MM were retrospectively reviewed. Acetazolamide was given at a dosage of 500 mg da

ily for 5 days starting two days before the predicted onset of the menstrual cycle as a short-term prophylactic treatment. VAS, MIDAS, and HIT assessments were performed before and after treatment. A total of 26 patients with PMM and 26 patients with MRM were identi�ed. After acetazolamide treatment, statistically signi�cant improvement was found in MIDAS, VAS and HIT scores in both groups of patients. The post-treatment MIDAS score was signi�cantly lower in the MRM group, but there was no signi�cant difference in post-treatment VAS and HIT scores between the groups. Using acetazolamide for short-term prophylaxis in patients with MM leads to decreased severity and frequency of headache and improvement in quality of life. The study is the �rst in the literature to use acetazolamide for short-term prophylaxis in patients diagnosed with MM. Keywords: menstrual migraine; acetazolamide; short-term prophylaxis; VAS; MIDAS; HITNeurology Asia 2021; 26(4) : 751 – 759Address correspondence to: Dr. Aysin Kisabay Ak, Assoc. Prof. Doctor of Neurology, Celal Bayar University, Manisa/Turkey 45000. Tel:+90 536 256 6809, email: aysinkisabay@hotmail.comDate of Submission: 16 May 2021; Date of Acceptance: 21 August 2021https://doi.org/10.54029/2021hmmINTRODUCTIONMigraine is a periodic, usually unilateral, throbbing type of headache accompanied by nausea and/or vomiting with onset in childhood The prevalence of migraine is highest at ages of 25 to 55 years in men as well as women; it is three times more common in The reasons for the more common occurrence of migraine in women include the presence of the menstrual cycle (MC) and hormonal changes. According to the International Classi�cation of Headache (ICHD-3) criteria, menstrual migraine (MM) is divided into two groups: pure menstrual migraine (PMM) and menstrually-related migraine (MRM). PMM occurs only during menstrual bleeding, whereas MRM may be seen in any period of the cycle as a consequence of hormonal MRM is seen in around 7% of the female population and 13% of women with migraine, whereas PMM is seen in about 2% of the female Decreased estrogen level in the late luteal phase has been shown to be the most important cause In addition, in�ammation is triggered as a consequence of decreased levels of magnesium and increased levels of prostaglandins, and migraine headache The present study aimed to evaluate and compare the severity of headache using a visual analog scale (VAS) and effects on quality of life using the Headache Impact Test (HIT) and Migraine Disability Assessment (MIDAS) tests before and after 3 months of treatment in both term prophylaxis of migraine. Patients diagnosed with MM are routinely given acetazolamide treatment for short-term prophylaxis in our centre. The patients presenting to the headache outpatient clinic of the Ne